Abstract |
Agonists of the 5-HT(2C) receptor have attracted much attention as therapeutic agents for the treatment of obesity. Subtype selectivity against other 5-HT(2) receptors is one of the most important prerequisites for reducing side effects. We present the synthesis of N-methyl-N-(1-methylpiperidin-4-yl)benzenesulfonamide analogs and their structure-activity relationship studies on 5-HT(2A) and 5-HT(2C) receptors. Although the compounds showed nanomolar activity to the 5-HT(2C) receptor, their selectivity against the 5-HT(2A) receptor was modest to low. Molecular modeling studies using homology modeling and docking simulation revealed that selectivity originated from subtype specific residues. The observed binding modes and receptor- ligand interactions provided us a clue for optimizing the selectivity against the 5-HT(2A) receptor.
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Authors | Jae Wan Jang, Je-Sook Baek, Gil Don Choi, Woo-Kyu Park, Yong Seo Cho, Du-Jong Baek, Ae Nim Pae |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 22
Issue 1
Pg. 347-52
(Jan 01 2012)
ISSN: 1464-3405 [Electronic] England |
PMID | 22153942
(Publication Type: Journal Article)
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Copyright | Copyright © 2011 Elsevier Ltd. All rights reserved. |
Chemical References |
- Ligands
- N-methyl-N-(1-methylpiperidin-4-yl)benzenesulfonamide
- Piperidines
- Receptor, Serotonin, 5-HT2C
- Sulfonamides
- Serotonin
- benzenesulfonamide
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Topics |
- Amino Acid Sequence
- Computer Simulation
- Drug Design
- Humans
- Inhibitory Concentration 50
- Ligands
- Models, Chemical
- Models, Molecular
- Molecular Conformation
- Molecular Sequence Data
- Piperidines
(chemical synthesis, pharmacology)
- Protein Binding
- Receptor, Serotonin, 5-HT2C
(chemistry, metabolism)
- Sequence Homology, Amino Acid
- Serotonin
(metabolism)
- Structure-Activity Relationship
- Sulfonamides
(chemical synthesis, pharmacology)
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